A Phase II Study of Cabozantinib in Patients With MET-Altered Lung Cancers

Only type I MET tyrosine kinase inhibitors (TKIs) are approved for treating MET-altered NSCLCs. Preclinically, type II TKIs, such as cabozantinib, can rescue progression on type I TKIs. This phase 2 trial (NCT01639508) evaluated the activity of cabozantinib in patients with MET-dependent lung cancers, including TKI-pretreated cancers.

This phase 2 trial with a Simon two-stage minimax design treated patients with metastatic, MET-altered lung cancers with cabozantinib (60 mg daily) until progression or intolerable toxicity. The primary end point was objective response rate (ORR). We prespecified that cabozantinib would be considered a useful agent if at least a 20% ORR was observed. Secondary end points included progression-free survival, overall survival, and safety.

We enrolled 28 patients, 23 patients (82%) with only a MET exon 14 alteration, two patients (7%) with MET amplification, and three patients (11%) with concurrent MET exon 14 alteration and amplification. There were 24 patients (86%) previously treated with a type I MET TKI. The ORR was 20% (5/25 assessable patients; 95% confidence interval [CI]: 8.9%-39.1%), with five partial responses (duration ranged from 4 to 39 mo). Four of five responders were type I MET TKI pretreated. The median progression-free survival and overall survival were 4.5 (95% CI: 3.3-5.7) months and 7.2 (95% CI: 2.9-11.5) months, respectively. Dose modification and discontinuation occurred in 64% (18/28) and 7% (2/28) of patients, respectively.

This trial met its primary end point. Importantly, we demonstrated that cabozantinib, a type II MET TKI, could benefit patients with MET-altered lung cancers previously treated with type I MET TKIs.